CD4+CD25+ T cell depletion impairs tolerance induction in a murine model of asthma.

BACKGROUND: Regulatory T cells (Tregs) are key players in controlling the development of airway inflammation. However, their role in the mechanisms leading to tolerance in established allergic asthma is unclear. OBJECTIVE: To examine the role of Tregs in tolerance induction in a murine model of asthma. METHODS: Ovalbumin (OVA) sensitized asthmatic mice were depleted or not of CD25(+) T cells by anti-CD25 PC61 monoclonal antibody (mAb) before intranasal treatment (INT) with OVA, then challenged with OVA aerosol. To further evaluate the respective regulatory activity of CD4(+)CD25(+) and CD4(+)CD25(-) T cells, both T cell subsets were transferred from tolerized or non-tolerized animals to asthmatic recipients. Bronchoalveolar lavage fluid (BALF), T cell proliferation and cytokine secretion were examined. RESULTS: Intranasal treatment with OVA led to increased levels of IL-10, TGF-beta and IL-17 in lung homogenates, inhibition of eosinophil recruitment into the BALF and antigen specific T cell hyporesponsiveness. CD4(+)CD25(+)Foxp3(+) T cells were markedly upregulated in lungs and suppressed in vitro and in vivo OVA-specific T cell responses. Depletion of CD25(+) cells before OVA INT severely hampered tolerance induction as indicated by a strong recruitment of eosinophils into BALF and a vigorous T cell response to OVA upon challenge. However, the transfer of CD4(+)CD25(-) T cells not only suppressed antigen specific T cell responsiveness but also significantly reduced eosinophil recruitment as opposed to CD4(+)CD25(+) T cells. As compared with control mice, a significantly higher proportion of CD4(+)CD25(-) T cells from OVA treated mice expressed mTGF-beta. CONCLUSION: Both CD4(+)CD25(+) and CD4(+)CD25(-) T cells appear to be essential to tolerance induction. The relationship between both subsets and the mechanisms of their regulatory activity will have to be further analyzed.

The Oncogene Metadherin Modulates the Apoptotic Pathway Based on the Tumor Necrosis Factor Superfamily Member TRAIL (Tumor Necrosis Factor-related Apoptosis-inducing Ligand) in Breast Cancer.

Metadherin (MTDH), the newly discovered gene, is overexpressed in more than 40% of breast cancers. Recent studies have revealed that MTDH favors an oncogenic course and chemoresistance. With a number of breast cancer cell lines and breast tumor samples, we found that the relative expression of MTDH correlated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in breast cancer. In this study, we found that knockdown of endogenous MTDH cells sensitized the MDA-MB-231 cells to TRAIL-induced apoptosis both in vitro and in vivo. Conversely, stable overexpression of MTDH in MCF-7 cells enhanced cell survival with TRAIL treatment. Mechanically, MTDH down-regulated caspase-8, decreased caspase-8 recruitment into the TRAIL death-inducing signaling complex, decreased caspase-3 and poly(ADP-ribose) polymerase-2 processing, increased Bcl-2 expression, and stimulated TRAIL-induced Akt phosphorylation, without altering death receptor status. In MDA-MB-231 breast cancer cells, sensitization to TRAIL upon MTDH down-regulation was inhibited by the caspase inhibitor Z-VAD-fmk (benzyloxycarbonyl-VAD-fluoromethyl ketone), suggesting that MTDH depletion stimulates activation of caspases. In MCF-7 breast cancer cells, resistance to TRAIL upon MTDH overexpression was abrogated by depletion of Bcl-2, suggesting that MTDH-induced Bcl-2 expression contributes to TRAIL resistance. We further confirmed that MTDH may control Bcl-2 expression partly by suppressing miR-16. Collectively, our results point to a protective function of MTDH against TRAIL-induced death, whereby it inhibits the intrinsic apoptosis pathway through miR-16-mediated Bcl-2 up-regulation and the extrinsic apoptosis pathway through caspase-8 down-regulation.

Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor.

PURPOSE: Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure. PATIENTS AND METHODS: Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P < .0001). Using -25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P < .0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P < .0001), primary resistance to imatinib (P = .024), or nongastric GIST (P = .002), regardless of the mutational status of the KIT and PDGFRA genes. CONCLUSION: Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.

A model of the wind direction signature in the Stokes emission vector from the ocean surface at microwave frequencies

This paper presents a model of the Stokes emission vector from the ocean surface. The ocean surface is described as an ensemble of facets with Cox and Munk's (1954) Gram-Charlier slope distribution. The study discusses the impact of different up-wind and cross-wind rms slopes, skewness, peakedness, foam cover models and atmospheric effects on the azimuthal variation of the Stokes vector, as well as the limitations of the model. Simulation results compare favorably, both in mean value and azimuthal dependence, with SSM/I data at 53° incidence angle and with JPL's WINDRAD measurements at incidence angles from 30° to 65°, and at wind speeds from 2.5 to 11 m/s.

De novo T cell generation and cell cycle analysis of CD4 and CD8 T cells during HIV-disease

RESUME POUR UN LARGE PUBLIC Parmi les globules blancs, les lymphocytes T 004 jouent un rôle primordial dans la coordination de la réponse immunitaire contre les pathogènes et les lymphocytes T CD8 dans leur élimination. Lors d'une infection par le virus de l'immunodéficience humaine (VIH-1), non seulement les cellules T CD4 sont les principales cibles d'infections, mais aussi elles disparaissent progressivement tout au long de la maladie. Ce phénomène, appelé aussi épuisement des lymphocytes T CD4, est la principale cause provoquant le Syndrome d'Immunodéficience Acquise (SIDA). Malgré de grands efforts de recherche, nous ne sommes toujours pas en mesure de dire si ce phénomène est dû à un défaut dans la production de nouvelles cellules ou à une destruction massive de cellules en circulation. Dans cette étude, nous nous proposions, dans un premier temps, de comparer la production de nouvelles cellules T CD4 et CD8 chez des individus VIH-négatifs et positifs. Les cellules nouvellement produites portent un marqueur commun que l'on appelle TREC et qui est facilement mesurable. En considérant des paramètres cliniques, nous étions en mesure de déterminer le niveau de TRECs de cellules T CD4 et CD8 dans différentes phases de la maladie. De là, nous avons pu déterminer que le niveau de TREC est toujours plus bas dans les cellules T CD8 de patients VIH-positifs comparativement à notre groupe contrôle. Nous avons pu déterminer par une analyse ultérieure que cette différence est due à une forte prolifération de ces cellules chez les patients VIH-positifs, ce qui a pour effet de diluer ce marqueur. En revanche, la production de nouvelles cellules T CD4 chez des patients VIH-positifs est accentuée lors de la phase précoce de la maladie et largement réprimée lors de la phase tardive. Dans un second temps, nous avons effectué une analyse à grande échelle de l'expression de gènes associés à la division cellulaire sur des lymphocytes T CD4 et CD8 d'individus VIH-¬positifs et négatifs, avec comme contrôle des cellules proliférant in vitro. De cette étude, nous avons pu conclure que les cellules T CD8 de patients VIH-positifs étaient en état de prolifération, alors que les lymphocytes T CD4 présentaient des défauts majeurs conduisant à un arrêt de la division cellulaire. Nos résultats montrent que la capacité à produire de nouvelles cellules chez des patients VIH¬positifs reste active longtemps pendant la maladie, mais que l'incapacité des cellules T CD4 à proliférer peut enrayer la reconstitution immunitaire chez ces individus. ABSTRACT The hallmark of HIV-1 infection is the depletion of CD4 T cells. Despite extensive investigation, the mechanisms responsible for the loss of CD4 T cells have been elucidated only partially. In particular, it remains controversial whether CD4 T cell depletion results from a defect in T cell production or from a massive peripheral destruction. In this study, de novo T cell generation has been investigated by measuring T cell receptor rearrangement excision circles (TRECs) on large cohorts of HIV-negative (N=120) and HIV-1 infected (N=298) individuals. Analysis of TREC levels was performed in HIV-infected subjects stratified by the stage of HIV disease based on CD4 T cell counts (early: >500 CD4 T cells/µl; intermediate: <500>200; late: <200) and by age (20 to 60 years, n = 259). Our data show that TREC levels in CD8 T cells were significantly lower in HIV-infected subjects at any stage of disease compared to the control group. In contrast, TREC levels in CD4 T cells were significantly higher in HIV-infected subjects at early stages disease while no significant differences were observed at intermediate stages of the disease and were severely reduced only at late stages of disease. To investigate further the status of cell cycle in peripheral CD4 and CD8 T cells in HIV-1 infections, we determined the pattern of gene expression with the microarray technology. In particular, CD4 and CD8 T cells of HIV-1 infected and HIV-negative subjects were analysed by Cell Cycle cDNA expression array. The patterns of gene expression were compared to in vitro stimulated CD4 and CD8 T cells and this analysis showed that CD8 T cells of HIV-1 infected subjects had a pattern of gene expression very similar to that of in vitro stimulated CD8 T cells thus indicating ongoing cell cycling. In contrast, CD4 T cells of HIV-1 infected subjects displayed a complex pattern of gene expression. In fact, CD4 T cells expressed high levels of genes typically associated with cell activation, but low levels of cell cycle genes. Therefore, these results indicated that activated CD4 T cells of HIV-1 infected subjects were in cell cycle arrest. Taking together these results indicate that thymus function is preserved for long time during HIV- 1 infection and the increase observed in early stage disease may represent a compensatory mechanism to the depletion of CD4 T cells. However, we provide evidence for a cell cycle arrest of peripheral CD4 T cells that may prevent potentially the replenishment of CD4 T cells. RESUME Les mécanismes responsables de la perte des lymphocytes T CD4 lors de l'infection pas VIH n'ont été élucidés que partiellement. Nous ne savons toujours pas si l'épuisement des lymphocytes T CD4 résulte d'un défaut dans la production de cellules ou d'une destruction périphérique massive. Dans cette étude, la production de cellules T a été étudiée en mesurant les cercles d'excision générés lors du réarrangement du récepteur au cellules T (TRECs) chez des individus VIH-négatifs (N=120) et VIH-1 positifs (N=298). L'analyse des niveaux de TREC a été faite chez sujets HIV-infectés en considérant les phases de la maladie sur la base des comptes CD4 (phase précoce: > 500 cellules CD4/µl; intermédiaire: < 500>200; tardive: < 200) et par âge. Nos données démontrent que les niveaux de TRECs des cellules T CD8 étaient significativement plus bas chez les sujets VIH-1 infectés, à tous les stades de la maladie comparativement au groupe contrôle. En revanche, les niveaux de TRECs des cellules T CD4 étaient significativement plus élevés chez les sujets VIH-1 infectés durant la phase précoce de la maladie, tandis qu'aucune différence significative n'était observée durant la phase intermédiaire et étaient très réduits dans la phase tardive. Dans une deuxième partie, nous avons utilisé la technique des biopuces à d'ADN complémentaire pour analyser la régulation du cycle cellulaire chez les lymphocytes T CD4 et CD8 périphériques lors d'une infection au VIH-1. Des profils d'expression ont été déterminés et comparés à ceux de cellules T CD4 et CD8 stimulées in vitro, démontrant que les cellules T CD8 des sujets VIH-positifs avaient un profil d'expression très semblable à celui des cellules stimulées in vitro en prolifération. En revanche, les lymphocytes T CD4 des sujets VIH-1 positifs avaient un profil d'expression de gène plus complexe. En fait, leur profil montrait une sur- expression de gènes associés à une activation cellulaire, mais une sous-expression de ceux induisant une division. Ainsi, ces résultats indiquent que les lymphocytes T CD4 d'individus VIH-positifs présentent des dérégulations qui conduisent à un arrêt du cycle cellulaire. Ces résultats montrent que la fonction thymique est préservée longtemps pendant l'infection au VIH-1 et que l'augmentation de la quantité de TRECs dans la phase précoce de la maladie peut représenter un mécanisme compensatoire à l'épuisement des cellules T CD4. Cependant, nous démontrons aussi un clair dysfonctionnement du cycle cellulaire chez les cellules T CD4 d'individus infectés par VIH-1 ce qui peut enrayer la reconstitution du système immunitaire.

Numerical Modelling of Combustion and Emission Formation in a Diesel Engine with Different Fuel Injection Characteristics

Päästöjen vähentäminen on ollut viime vuosina tärkeässä osassa polttomoottoreita kehitettäessä.Monet viralliset tahot asettavat uusia tiukempia päästörajoituksia. Päästörajatovat tyypillisesti olleet tiukimmat autoteollisuuden valmistamille pienille nopeakäyntisille diesel-moottoreille, mutta viime aikoina paineita on kohdistunut myös suurempiin keskinopeisiin ja hidaskäyntisiin diesel-moottoreihin. Päästörajat ovat erilaisia riippuen moottorin tyypistä, käytetystä polttoaineesta ja paikasta missä moottoria käytetään johtuen erilaisista paikallisista laeista ja asetuksista. Eniten huomiota diesel-moottorin päästöissä täytyy kohdistaa typen oksideihin, savun muodostukseen sekä partikkeleihin. Laskennallisen virtausmekaniikan (CFD) avulla on hyvät mahdollisuudet tutkia diesel-moottorin sylinterissä tapahtuvia ilmiöitä palamisen aikana. CFD on hyödyllinen työkalu arvioitaessa moottorin suorituskykyä ja päästöjen muodostumista. CFD:llä on mahdollista testata erilaisten parametrien ja geometrioiden vaikutusta ilman kalliita moottorinkoeajoja. CFD:tä voidaan käyttää myös opetustarkoituksessa lisäämään paloprosessin tuntemusta. Tulevaisuudessa palamissimuloinnit CFD:llä tulevat epäilemättä olemaan tärkeä osa moottorin kehityksessä. Tässä diplomityössä on tehty palamissimuloinnit kahteen erilaisilla poittoaineenruiskutuslaitteistoilla varustettuun Wärtsilän keskinopeaan diesel-moottoriin. W46 moottorin ruiskutuslaitteisto on perinteinen mekaanisesti ohjattu pumppusuutin ja W46-CR moottorissa on elektronisesti ohjattu 'common rail' ruiskutuslaitteisto. Näiden moottorien ja käytössä olevien ruiskutusprofiilien lisäksi on simuloinneilla testattu erilaisia uusia ruiskutusprofiileja, jotta erityyppisten profiilien hyvät ja huonot ominaisuudet tulisivat selville. Matalalla kuormalla kiinnostuksen kohteena on nokipäästöjen muodostus ja täydellä kuormalla NOx-päästöjen muodostus ja polttoaineen kulutus. Simulointien tulokset osoittivat, että noen muodostusta matalalla kuormalla voidaan selvästi vähentää monivaiheisella ruiskutuksella, jossa yksi ruiskutusjakso jaetaan kahteen tai useampaan jaksoon. Erityisen tehokas noen vähentämisessä vaikuttaa olevan ns. jälkiruiskutus (post injection). Matalat NOx-päästöt ja hyvä polttoaineen kulutus täydellä kuormalla on mahdollista saavuttaaasteittain nostettavalla ruiskutusnopeudella.

Development of the Acoustic Emission Based Diagnostics Concept for the Rotary Lime Kiln

Reaaliaikainen, ennakoiva kunnonvalvonta on erittäin tärkeä osa modernin tehtaan tai tuotantolinjan toimintaa. Diplomityön teettäjä haluaa edelleen kehittää akustiseen emissioon perustuvaa kunnonvalvonta järjestelmäänsä, jotta siitä olisi enemmän hyötyä asiakkaalle. Diplomityö sisältää johdannonakustiseen emissioon ja akustisiin emissio sensoreihin. Työn tavoitteena oli kehittää päätöksentekojärjestelmä, jota käytettäisiin työn teettäjän valmistamien sensoreiden antaman tiedon automatisoituun analysointiin. Työssä on vertailtu kolmea eri ohjelmistotoimittajaa ja heidän ohjelmiaan, ja tehty ehdotus hankittavasta ohjelmistosta. Lisäksi työssä on kehitetty ohjeita, joiden avulla ohjelmisto ohjelmoidaan tuottamaan reaaliaikaista tietoa ja huolto-ohjeita sen käyttäjille. Lisäksi työssä annetaan ehdotuksia kunnonvalvonta- ja päätöksentekojärjestelmän edelleen kehittämiseen.

Self-Organising Maps and Correlation Analysis as a Tool to Explore Patterns in Excitation-Emission Matrix Data Sets and to Discriminate Dissolved Organic Matter Fluorescence Components

Dissolved organic matter (DOM) is a complex mixture of organic compounds, ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means of Excitation-Emission Matrices (EEM), has become an indispensable tool to study DOM sources, transport and fate in aquatic ecosystems. However the statistical treatment of large and heterogeneous EEM data sets still represents an important challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern recognition method which clusterizes and reduces the dimensionality of input EEMs without relying on any assumption about the data structure. In this paper, we show how SOM, coupled with a correlation analysis of the component planes, can be used both to explore patterns among samples, as well as to identify individual fluorescence components. We analysed a large and heterogeneous EEM data set, including samples from a river catchment collected under a range of hydrological conditions, along a 60-km downstream gradient, and under the influence of different degrees of anthropogenic impact. According to our results, chemical industry effluents appeared to have unique and distinctive spectral characteristics. On the other hand, river samples collected under flash flood conditions showed homogeneous EEM shapes. The correlation analysis of the component planes suggested the presence of four fluorescence components, consistent with DOM components previously described in the literature. A remarkable strength of this methodology was that outlier samples appeared naturally integrated in the analysis. We conclude that SOM coupled with a correlation analysis procedure is a promising tool for studying large and heterogeneous EEM data sets.

Technical Note: Dissolved organic matter fluorescence a finite mixture approach to deconvolve excitation-emission matrices

The analysis of the shape of excitation-emission matrices (EEMs) is a relevant tool for exploring the origin, transport and fate of dissolved organic matter (DOM) in aquatic ecosystems. Within this context, the decomposition of EEMs is acquiring a notable relevance. A simple mathematical algorithm that automatically deconvolves individual EEMs is described, creating new possibilities for the comparison of DOM fluorescence properties and EEMs that are very different from each other. A mixture model approach is adopted to decompose complex surfaces into sub-peaks. The laplacian operator and the Nelder-Mead optimisation algorithm are implemented to individuate and automatically locate potential peaks in the EEM landscape. The EEMs of a simple artificial mixture of fluorophores and DOM samples collected in a Mediterranean river are used to describe the model application and to illustrate a strategy that optimises the search for the optimal output.

Mid-gut ACTH-secreting neuroendocrine tumor unmasked with (18)F-dihydroxyphenylalanine-positron emission tomography.

Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and (18)F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor. (18)F-dihydroxyphenylalanine (F-DOPA)-PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization. LEARNING POINTS: Uncontrolled high cortisol levels in EAS can be lethal if untreated.Surgical excision is the keystone of NETs treatment, thus tumor localization is crucial.Most cases of EAS are caused by NETs, which are located mainly in the lungs. However, small gut NETs are elusive to conventional imaging and require metabolic imaging for detection.FDG-PET, based on tumor high metabolic rate, may not detect NETs that have low mitotic activity. SSRS may also fail, due to absent or low concentration of SST2, which may be down regulated by excess cortisol.F-DOPA-PET, based on amine-precursor uptake, can be a useful method to localize the occult source of ACTH in EAS when other methods have failed.

Emission Trading and Tradable Green Certificates Impacts on the Business Activity of Vattenfall Oy

Ihmisen toiminnan vaikutus ilmakehään johtaa todennäköisesti ilmastonmuutoksiin. Eräs näistä muutoksista on maapallon keskilämpötilan nousu, joka aiheutuu kasvihuonekaasujen lisääntyneestä pitoisuudesta ilmakehässä. Vaikutusten vähentämiseksi on hiilidioksidipäästöjä vähennettävä. Kioton pöytäkirja asettaa allekirjoittaneille maille päästövelvoitteet. Euroopan unionin tulee vähentää kasvihuonekaasupäästöjään 8%:lla. Eräs vähennysmekanismeista on päästökauppa. Päästökauppa on sekä keino suojella ympäristöä että ympäristöpoliittinen instrumentti kasvihuonekaasupäästövähennysten kustannusten keventämiseksi. Päästökauppa ei suoranaisesti vähennä kasvihuonekaasupäästöjä, vaan tasaa niitä maiden ja laitosten välillä. Uusiutuvan energian käytön edistäminen sekä kansainvälisesti että kansallisesti johtaa suoriin kasvihuonekaasupäästöjen vähenemiseen. Euroopan unionin jäsenvaltiot ovat asettaneet kansalliset viitearvot uusituvan sähkön kulutukselle. Saavuttaakseen nämä viitearvot maiden tulee tukea uusiutuvia energialähteitä eri menetelmin kuten vihreillä sertifikaateilla. Päästökauppa ja kaupattavat vihreät sertifikaatit tulevat vaikuttamaan energiantuottajien liiketoimintaan. Työssä on tutkittu päästökaupan ja vihreiden sertifikaattien vaikutuksia Vattenfall Kaukolämpö Oy:n, Vattenfall Sähköntuotanto Oy:n ja Vamy Oy:n liiketoimintaan.

Dynamic and quasistatic trajectories in quasifission reactions and particle emission

We show that the quasifission paths predicted by the one-body dissipation dynamics, in the slowest phase of a binary reaction, follow a quasistatic path, which represents a sequence of states of thermal equilibrium at a fixed value of the deformation coordinate. This establishes the use of the statistical particle-evaporation model in the case of dynamical time-evolving systems. Pre- and post-scission multiplicities of neutrons and total multiplicities of protons and α particles in fission reactions of 63Cu+92Mo, 60Ni+100Mo, 63Cu+100Mo at 10 MeV/u and 20Ne+144,148,154Sm at 20 MeV/u are reproduced reasonably well with statistical model calculations performed along dynamic trajectories whose slow stage (from the most compact configuration up to the point where the neck starts to develop) lasts some 35×10−21 s.

Unification of Emission Measurements in Paper and Pulp Mills

Tässä diplomityössä tavoitteena on selvittää käytännöt ja menetelmät, joilla UPM-Kymmenen sellu-, paperi- ja vaneritehtaat ympäri maailman mittaavat ja laskevat ilmapäästönsä. Tämä tehdään kyselylomakkeella, joka lähetetään tehtaiden ympäristöpäälliköille. Kaikki tärkeimmät seikat ilmapäästöihin liittyen, kuten vaaditut jatkuvatoimiset mittaukset, jaksottaiset mittaukset, raportointikäytäntö, kalibrointi jne. kysytään lomakkeessa. Kyselylomakkeessa painotetaan mittauskäytäntöä sellutehtaissa sekä energiantuotannossa. Saatujen tulosten perusteella annetaan ehdotuksia sekä ohjeita tulevaisuutta varten, jotta mittaustulosten kokoaminen helpottuisi ja vertailukelpoisuus paranisi. Työn kirjallisuusosuudessa selvitetään yleisimmät päästölähteet sekä päästökomponentit paperi –ja selluteollisuudessa. Näiden ei toivottujen yhdisteiden syntymekanismit sekä menetelmät niiden poistamiseksi savukaasuista on myös lyhyesti kuvailtu. Myös erilaiset analysointi- ja näytteenottomenetelmät on kerrottu. Erot tehtaiden ympäristöluvissa käydään läpi, jakaen tehtaat kolmeen maantieteelliseen ryhmään. Lupakäytäntöjen osalta Suomen osuutta on painotettu, sillä UPM-Kymmene on varsin Suomikeskeinen yhtiö tehtaiden lukumääriin ja sijainteihin katsottuna. Viranomaismääräykset sekä päästörajat muutamista tehtaista on esitetty havainnollistaakseen alueellisia eroja.

Quantitative proteomics of heat-treated human cells show an across-the-board mild depletion of housekeeping proteins to massively accumulate few HSPs.

Classic semiquantitative proteomic methods have shown that all organisms respond to a mild heat shock by an apparent massive accumulation of a small set of proteins, named heat-shock proteins (HSPs) and a concomitant slowing down in the synthesis of the other proteins. Yet unexplained, the increased levels of HSP messenger RNAs (mRNAs) may exceed 100 times the ensuing relative levels of HSP proteins. We used here high-throughput quantitative proteomics and targeted mRNA quantification to estimate in human cell cultures the mass and copy numbers of the most abundant proteins that become significantly accumulated, depleted, or unchanged during and following 4 h at 41 °C, which we define as mild heat shock. This treatment caused a minor across-the-board mass loss in many housekeeping proteins, which was matched by a mass gain in a few HSPs, predominantly cytosolic HSPCs (HSP90s) and HSPA8 (HSC70). As the mRNAs of the heat-depleted proteins were not significantly degraded and less ribosomes were recruited by excess new HSP mRNAs, the mild depletion of the many housekeeping proteins during heat shock was attributed to their slower replenishment. This differential protein expression pattern was reproduced by isothermal treatments with Hsp90 inhibitors. Unexpectedly, heat-treated cells accumulated 55 times more new molecules of HSPA8 (HSC70) than of the acknowledged heat-inducible isoform HSPA1A (HSP70), implying that when expressed as net copy number differences, rather than as mere "fold change" ratios, new biologically relevant information can be extracted from quantitative proteomic data. Raw data are available via ProteomeXchange with identifier PXD001666.